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1.
Biomed Pharmacother ; 125: 109978, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058220

RESUMO

Severe acute pancreatitis (SAP), a critical inflammatory pathological disease of the pancreas, is crucial for the manifestation of lethal multiple organ dysfunction syndrome and systemic inflammatory response syndrome. Acute kidney injury (AKI) is one of the most severe complications of severe acute pancreatitis. Yet, the specific pathogenesis of AKI following SAP is defectively understood, and involves in multiple pathological processes in a "network-regulative" pattern, including dysfunction of the intestinal barrier, prolonged activation of coagulation, elevated discharge of damage-associated molecular patterns, complication of abdominal compartment syndrome, excessive release of inflammatory mediators, overexpression of procalcitonin, and incitement of chronic metabolic diseases. Therefore, in this review, we summarize the current knowledge on the pathogenesis of kidney injury following SAP to provide a better understanding of the interactions involved and to encourage the identification of novel targeted therapies to treat SAP and associated AKI.

2.
Clin Chem Lab Med ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32069228

RESUMO

Background The complete blood count (CBC) is a basic test routinely ordered by physicians as a part of initial diagnostic work-up on their patients. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are needed to establish analytical performance specifications. Our aim was to define the BV of CBC parameters using a rigorous protocol that is compliant with the Biological Variation Data Critical Appraisal Checklist (BIVAC) provided by the European Federation of Clinical Chemistry and Laboratory Medicine. Methods Blood samples drawn from 41 healthy Chinese subjects (22 females and 19 males; 23-59 years of age) once monthly for 6 consecutive months were analyzed using an ABX Pentra 80 instrument. The instrument was precisely calibrated. All samples were analyzed in duplicate for 13 CBC parameters. The data were assessed for outliers, normality, and variance homogeneity prior to nested ANOVA. Gender-stratified within-subject (CVI) and between-subject (CVG) BV estimates were calculated. Results The number of remaining data for each subject was 442-484 after removing outliers. No significant differences existed between female/male CVI estimates. Except for leukocytes, neutrophils, and lymphocytes, the mean values of 10 parameters differed significantly between genders, rendering partitioning of CVG data between genders. No significant differences were detected between most BV estimates and recently published estimates representing a Europid population. Conclusions Most BV estimates in BIVAC-compliant studies are similar. The turnover time of blood cells and age distribution of participants should be considered in a CBC BV study. Our study will contribute to global BV estimates and future studies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32003210

RESUMO

For the first time, we report the successful fabrication of well-behaved field-effect transistors based on Nb-doped ß-Ga2O3 nanobelts mechanically exfoliated from bulk single crystals. The exfoliated ß-Ga2O3 nanobelts were transferred onto a purified surface of the 110 nm SiO2/Si substrate. These Nb-doped devices showed excellent electrical performance such as an ultrasmall cutoff current of ∼10 fA, a high current on/off ratio of >108, and a quite steep subthreshold swing (SS, ∼120 mV/decade). Furthermore, we investigated the temperature dependence down to 200 K, providing insightful information for its operation in a harsh environment. This work lays a foundation for wider application of Nb-doped ß-Ga2O3 in nano-electronics.

4.
Dig Dis Sci ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020360

RESUMO

BACKGROUND: Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. AIM: To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. METHODS: This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. RESULTS: From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1-100%) and without bismuth = 94.7% (90/95, 95% CI 90.3-99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2-96.2%) versus 88.9% (96/108, 95% CI 82.8-95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. CONCLUSION: Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.

5.
Eur Radiol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065280

RESUMO

The original version of this article, published on 03 January 2020, unfortunately contained two mistakes.

6.
BMC Anesthesiol ; 20(1): 39, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024465

RESUMO

BACKGROUND: The comparative efficacy of epidural bupivacaine alone and bupivacaine combined with magnesium sulfate in providing postoperative analgesia remains controversial. METHODS: We searched Mediline (OvidSP), EMBASE (OvidSP) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify trials that compared epidural bupivacaine and magnesium sulfate combination (intervention) with bupivacaine alone (control). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to assess the quality of evidence. RESULTS: Eleven studies fulfilled our inclusion criteria after screening. We found that epidural bupivacaine combined with magnesium sulfate could prolong the time for first rescue analgesics (SMD 4.96; 95% CI [2.75, 7.17], P < 0.00001, I2 = 98%), reduce the number of patients who need rescue analgesics (RR 0.38; 95% CI [0.20, 0.74], P = 0.004, I2 = 75%) and requirement for rescue analgesics (SMD -2.65; 95% CI [- 4.23, - 1.06], P = 0.001, I2 = 96%). CONCLUSIONS: Magnesium suifate as an adjuvant of epidural bupivacaine improved postoperative analgesia. However, we rated the quality of evidence to be very low because of high heterogeneity, imprecise of results and small sample sizes. Furthermore, further large high-quality trials are still needed to confirm the effects of magnesium sulfate on postoperative analgesia.

7.
Sci Rep ; 10(1): 2150, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034252

RESUMO

Intravascular optical coherence tomography (IVOCT) is used to assess stent tissue coverage and malapposition in stent evaluation trials. We developed the OCT Image Visualization and Analysis Toolkit for Stent (OCTivat-Stent), for highly automated analysis of IVOCT pullbacks. Algorithms automatically detected the guidewire, lumen boundary, and stent struts; determined the presence of tissue coverage for each strut; and estimated the stent contour for comparison of stent and lumen area. Strut-level tissue thickness, tissue coverage area, and malapposition area were automatically quantified. The software was used to analyze 292 stent pullbacks. The concordance-correlation-coefficients of automatically measured stent and lumen areas and independent manual measurements were 0.97 and 0.99, respectively. Eleven percent of struts were missed by the software and some artifacts were miscalled as struts giving 1% false-positive strut detection. Eighty-two percent of uncovered struts and 99% of covered struts were labeled correctly, as compared to manual analysis. Using the highly automated software, analysis was harmonized, leading to a reduction of inter-observer variability by 30%. With software assistance, analysis time for a full stent analysis was reduced to less than 30 minutes. Application of this software to stent evaluation trials should enable faster, more reliable analysis with improved statistical power for comparing designs.

8.
Gen Physiol Biophys ; 39(1): 49-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039824

RESUMO

As a naturally occurring flavone, luteolin has received much attention due to its antioxidant, anti-inflammatory and anticancer functions. In the present study, we investigated the effect of luteolin on colonic motility and its mechanism using isometric muscle recording and the whole-cell patch-clamp technique in mice. Luteolin dose-dependently inhibited colonic smooth muscles motility and CMMC significantly. BayK8644, an L-type Ca2+ channel agonist, significantly attenuated the luteolin-induced inhibition. Moreover, the calcium currents recorded in colonic smooth muscle cells were dramatically inhibited by luteolin. However, no significant changes were found in the luteolin-induced inhibitory effect in the presence of TEA, a nonselective K+ channel blocker, glibenclamide, an ATP-dependent K+ channel blocker, and apamin, a small-conductance Ca2+-activated K+ channel blocker. Additionally, luteolin did not affect potassium currents. Furthermore, TTX, a Na+ channel blocker, L-NAME, an inhibitor of nitric oxide (NO) synthase, ODQ, an inhibitor of NO-sensitive guanylyl cyclase, and Ani9, a specific ANO1 channels blocker, had no effect on the luteolin-induced suppression. These results suggest that luteolin inhibited colonic smooth muscle motility by inhibiting L-type calcium channels in mice but not through potassium channels, the enteric nervous system (ENS), NO signaling pathways or ANO1 channels of interstitial cells of Cajal (ICCs).

9.
Chin Med J (Engl) ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044816

RESUMO

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost, and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity, and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the logistic regression were cardiac troponin T (CTnT) (coefficient = 0.346, OR = 1.413), temperature (T) (coefficient = 0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206, OR = 0.814), serum kalium (K) (coefficient = 0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient = -0.101, OR = 0.904), and albumin (ALB) (coefficient = -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heart rate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB, and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

10.
Ophthalmic Res ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32079013

RESUMO

INTRODUCTION: Post-trabeculectomy scaring due to excessive proliferation of human Tenon's fibroblasts (HTFs) often led to operation failure. Developing a new anti-fibrosis drug with high efficacy to inhibit HTFs' cell growth will greatly improve the effectiveness of trabeculectomy. OBJECTIVE: This study aims to investigate the effect of berbamine (BBM) treatment on the cell growth and survival of HTFs. METHODS: Cultured human fetal Tenon's fibroblasts (HFTFs) were treated with or without different concentrations of BBM. Cell morphology was observed with a phase contrast microscope. A CCK-8 method and Ki67 immunofluorescence were used to determine cell viability and cell proliferation. A scratch test was used to study cell migration. Flow cytometry and TUNEL staining were performed to detect cell apoptosis. The expression of BAX/BCL-2, ERK and AKT/mTOR pathway components was determined by western blotting. RESULTS: BBM treatment disrupted HFTF's normal morphology and inhibited its cell growth in a dose-dependent manner. Ki67 immunofluorescence and scratch assay showed BBM suppressed HFTF's cell proliferation and migration. Importantly, BBM dose-dependently increased the BAX/BCL-2 ratio and induced apoptosis in HFTF cells. Western blotting showed BBM significantly inhibited the ERK and AKT/mTOR pathway, and PTEN inhibition ameliorates the inhibitory effect of BBM on cell viability and survival in HFTFs. CONCLUSIONS: BBM potently inhibits the cell growth and survival of HTFs through AKT/mTOR and has the potential to serve as an anti-fibrosis drug after trabeculectomy.

11.
Life Sci ; 244: 117343, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31978449

RESUMO

AIMS: Epithelial-mesenchymal transition (EMT) is one of the important regulators of metastasis in advanced hepatocellular carcinoma (HCC). Blocking the Notch signaling pathway and then reversing the EMT process is a hot spot in clinical tumor research. Here, we aimed to investigate the effect and underlying mechanisms of ADAM-17 (a key cleavage enzyme of Notch pathway) inhibitor ZLDI-8 we found before on the metastasis of hepatocellular carcinoma in vitro and in vivo. MAIN METHODS: The cell viability of HCC cells was evaluated by MTT and colony formation assays. Migration and invasion were assessed respectively with wound healing and transwell assays. The expression and location of proteins were detected by western blot and immunofluorescence, respectively. The effects of ZLDI-8 on metastasis of liver cancer in vivo were investigated in a tail vein injection model. KEY FINDINGS: In the present work, ZLDI-8 significantly inhibited proliferation, migration, invasion and EMT phenotype of highly aggressive MHCC97-H and LM3 cells. Moreover, ZLDI-8 could inhibit the migration and invasion of HepG2 and Bel7402 cells induced by TGF-ß1. ZLDI-8 suppressed the protein expression of interstitial markers and increased that of epithelial markers. Meanwhile, ZLDI-8 decreased the expression of proteins in the Notch signaling pathway. Finally, ZLDI-8 blocks metastasis in the lung metastasis model in vivo. SIGNIFICANCE: ZLDI-8 suppressed the metastasis of hepatocellular carcinoma, which was associated with reversing the EMT process and regulating Notch signaling pathway. The study laid the foundation for the discovery of drugs that reverse EMT to inhibit advanced HCC metastasis.


Assuntos
Proteína ADAM17/antagonistas & inibidores , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Apoptose , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Proliferação de Células , Humanos , Técnicas In Vitro , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Artigo em Inglês | MEDLINE | ID: mdl-31948864

RESUMO

OBJECTIVE: To describe the population-level risk of infant and maternal outcomes for women who experience imprisonment and compare outcomes with the general population. METHODS: We conducted a retrospective cohort study. We used linked correctional and health data for women released from provincial prisons in 2010. We defined three exposure groups for Ontario singleton deliveries from 2005-2015: deliveries to women who were in prison during pregnancy but not necessarily for delivery, prison pregnancies; deliveries to women who had been in prison but not while pregnant, prison controls; and general population deliveries. We compared groups using generalized estimating equations. Primary outcomes were preterm birth, low birth weight, and small for gestational age birth weight. Secondary outcomes included NICU admission, neonatal abstinence syndrome, placental abruption, and preterm prelabour rupture of membranes. RESULTS: In prison pregnancies (N = 544) and prison controls (N = 2156), respectively, preterm birth risk was 15.5% and 12.5%, low birth weight risk was 13.0% and 11.6%, and small for gestational age birth weight risk was 18.1% and 19.2%. Adjusted for maternal age and parity and compared with general population deliveries (N = 1 284 949), odds ratios were increased for prison pregnancies and prison controls, respectively, at 2.7 (95% CI 2.2-3.4) and 2.1 (95% CI 1.9-2.4) for preterm birth, 3.1 (95% CI 2.4-3.9) and 2.7 (95% CI 2.3-3.1) for low birth weight, and 1.6 (95% CI 1.3-2.1) and 1.8 (95% CI 1.6-2.0) for small for gestational age birth weight. CONCLUSION: There is an increased risk of adverse infant outcomes in women who experience imprisonment compared with the general population, whether they are in prison during pregnancy or not.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31919567

RESUMO

PURPOSE: The impact of myeloid sarcoma (MS) on clinical outcome of pediatric acute myeloid leukemia (AML) patients remains controversial. Moreover, little is known about the role of stem cell transplantation (SCT) in such patients. METHODS: Clinical data of patients with AML under 18 years of age were retrieved from the TARGET dataset. We analyzed the prevalence, clinical profile, molecular characteristics, and prognosis of MS in these patients. RESULTS: Among 884 pediatric patients with AML, the frequency of MS was 12.3%. Pediatric AML with MS was associated with age under 1-year, abnormal cytogenetics, and KMT2A rearrangement. Moreover, MS was associated with a low complete remission rate, high induction death, poor 5-year EFS, and OS. KMT2A rearrangement had a negative impact on clinical outcome in AML patients with MS. In addition, SCT had no significant effect on the survival of AML patients with MS. Multivariate analysis revealed that MS was an unfavorable prognostic factor in pediatric AML in terms of EFS (Hazard ratio 1.670, P < 0.001) and OS (Hazard ratio 1.623, P = 0.004). CONCLUSIONS: The presence of MS at diagnosis of pediatric AML is associated with poor clinical outcomes, particularly when associated with KMT2A rearrangements. Moreover, pediatric patients with AML and MS may not benefit from SCT.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 53-57, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948525

RESUMO

OBJECTIVE: To study the changes in the serum levels of Chemerin and Omentin-1 in children with Kawasaki disease (KD) in the acute stage after intravenous immunoglobulin (IVIG) treatment and related clinical significance. METHODS: A total of 60 children who were diagnosed with KD from January 2015 to April 2019 were enrolled as subjects. Forty healthy children and 40 children with acute infectious diseases were enrolled as the healthy control group and the infection control group respectively. According to the sensitivity to IVIG treatment, the children with KD were divided into an IVIG sensitive group with 51 children and a non-IVIG sensitive group with 9 children. According to the presence or absence of coronary artery lesion, the children with KD were divided into a CAL group with 13 children and a non-CAL group with 47 children. ELISA was used to measure the serum levels of Omentin-1 and Chemerin before and after the treatment. RESULTS: The children with KD had significantly higher serum levels of Chemerin and Omentin-1 than the healthy control and infection control groups before treatment (P<0.05). After 48 hours of treatment, the IVIG sensitive group had a significant reduction in the serum level of Chemerin (P<0.05), while there was no significant change in the serum level of Omentin-1 after treatment (P>0.05). Before treatment, the non-IVIG sensitive group had a significantly higher serum level of Chemerin than the IVIG sensitive group (P<0.05), and the CAL group had a significantly higher serum level of Chemerin than the non-CAL group, while there was no significant difference in the serum level of Omentin-1 between the IVIG sensitive and non-IVIG sensitive groups, as well as between the CAL and non-CAL groups (P>0.05). CONCLUSIONS: High serum levels of Chemerin and Omentin-1 may play an important role in the development and progression of KD. Chemerin may be involved in the development of CAL in children with KD. The serum level of Chemerin may be used as a new index for predicting the sensitivity to IVIG treatment.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Adipocinas , Quimiocinas , Criança , Doença da Artéria Coronariana , Humanos , Imunoglobulinas Intravenosas
15.
ACS Appl Mater Interfaces ; 12(6): 7833-7839, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31961648

RESUMO

Recently, neuromorphic devices have been receiving increasing interest in the field of artificial intelligence (AI). Realization of fundamental synaptic plasticities on hard-ware devices would endow new intensions for neuromorphic devices. Spike-rate-dependent plasticity (SRDP) is one of the most important synaptic learning mechanisms in brain cognitive behaviors. It is thus interesting to mimic the SRDP behaviors on solid-state neuromorphic devices. In the present work, nanogranular phosphorus silicate glass (PSG)-based proton conductive electrolyte-gated oxide neuromorphic transistors have been proposed. The oxide neuromorphic transistors have good transistor performances and frequency-dependent synaptic plasticity behavior. Moreover, the neuromorphic transistor exhibits SRDP activities. Interestingly, by introducing priming synaptic stimuli, the modulation of threshold frequency value distinguishing synaptic potentiation from synaptic depression is realized for the first time on an electrolyte-gated neuromorphic transistor. Such a mechanism can be well understood with interfacial proton gating effects of the nanogranular PSG-based electrolyte. Furthermore, the effects of SRDP learning rules on pattern learning and memory behaviors have been conceptually demonstrated. The proposed neuromorphic transistors have potential applications in neuromorphic engineering.

16.
Chem Biol Interact ; 317: 108960, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31981573

RESUMO

Tripartite motif (TRIM) protein family is a group of proteins, which belongs to RING family of ubiquitin E3 ligases. TRIM proteins are involved in oncogenesis, while the roles in different cancers are controversial. However, the expression pattern and biological functions of TRIM47 in breast cancer remain unclear. In the present study, we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer. TRIM47 was found to be significantly up-regulated in breast cancer tissues and cell lines. TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation, migration, and invasion. Besides, TRIM47 knockdown regulated the expressions of the epithelial-mesenchymal transition (EMT)-related markers including increase in E-cadherin, and decrease in N-cadherin, vimentin and Snail. Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth in vivo. Furthermore, TRIM47 knockdown markedly inhibited the activation of PI3K/Akt signaling pathway, while the effects of TRIM47 knockdown were reversed by the treatment of insulin-like growth factor-1 (IGF-1), which is an activator of PI3K/Akt. Taken together, the findings indicated that knockdown of TRIM47 suppressed tumorigenesis and progression of breast cancer through the inhibition of PI3K/Akt pathway, and suggested that TRIM47 might be a potential therapy target for breast cancer treatment.

17.
Blood Cancer J ; 10(1): 1, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31915364

RESUMO

Studies on the clinical significance of Nucleophosmin (NPM1) mutations in pediatric AML in a large cohort are lacking. Moreover, the prognosis of patients with co-occurring NPM1 and FLT3/ITD mutations is controversial. Here, we analyzed the impact of NPM1 mutations on prognoses of 869 pediatric AML patients from the TAGET dataset. The frequency of NPM1 mutations was 7.6%. NPM1 mutations were significantly associated with older age (P < 0.001), normal cytogenetics (P < 0.001), FLT3/ITD mutations (P < 0.001), and high complete remission induction rates (P < 0.05). Overall, NPM1-mutated patients had a significantly better 5-year EFS (P = 0.001) and OS (P = 0.016) compared to NPM1 wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant effect on the survival of patients with both NPM1 and FLT3/ITD mutations. Multivariate analysis revealed that NPM1 mutations were independent predictors of better outcome in terms of EFS (P = 0.004) and OS (P = 0.012). Our findings showed that NPM1 mutations confer an independent favorable prognostic impact in pediatric AML despite of FLT3/ITD mutations. In addition, pediatric AML patients with both NPM1 and FLT3/ITD mutations appear to have favorable prognoses and may not need hematopoietic stem cell transplantations.

19.
Eur Radiol ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900700

RESUMO

OBJECTIVES: To identify the relationship between human epidermal growth factor receptor 2 (HER2) status and cone-beam breast CT (CBBCT) characteristics in surgically resected breast cancer. METHODS: Preoperative CBBCT of patients with BI-RADS 4 or 5 lesions identified on mammography or ultrasound and dense or very dense breast tissue were retrospectively evaluated in 181 surgically resected breast cancer (triple-negative excluded) between May 2012 and November 2014. A set of CBBCT descriptors was semiquantitatively assessed by consensus double reading. Reader reproducibility was analyzed. Multivariable logistic regression analysis using backward elimination (BEA) with the Wald criterion was performed to identify independent predictive factors of harboring HER2/neu. Principle component analysis (PCA) was used to determine characteristics that might differentiate HER2 status. Receiver operating characteristic (ROC) curve analyses were conducted to determine the predictive capability. RESULTS: HER2 positive was found in 101 (55.8%) of 181 patients. Inter-observer agreement was high for characteristics' assessment. Based on BEA, pathologic grade, maximum dimension, lobulation, ΔCT, and calcification morphology were confirmed as independent predictive factors of HER2/neu overexpression. PCA showed that calcification- and border-related characteristics were the most important for differentiation. ROC curve analyses showed that CBBCT features (AUC = 0.853) were superior to clinicopathologic features (AUC = 0.613, p < 0.001) and comparable with combination (AUC = 0.856, p = 0.866). CONCLUSIONS: CBBCT features could be used to prognosticate HER2 status independently, which are potentially complementary to histopathologic result and helpful in guiding biopsy. KEY POINTS: • Dmax, lobulation, ΔCT, and calcification morphology are independent predictors of HER2 status. • CBBCT features are superior to clinicopathologic features in HER2+/- discrimination. • CBBCT features are comparable with combination with clinicopathologic features in HER2+/- discrimination.

20.
J Ethnopharmacol ; 249: 112433, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31783135

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aß cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aß. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3ß and triggering hyperphosphorylation of tau. The Aß levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aß contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 µg/mL) significantly inhibited the secretion and production of Aß in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aß, IL-1ß and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aß cascade, tau pathology and neuroinflammation in vitro and in vivo.

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